IgE-Associated IGHV Genes from Venom and Peanut Allergic Individuals Lack Mutational Evidence of Antigen Selection

Wang, Yan, Jackson, Katherine J. L., Davies, Janet, Chen, Zhiliang, Gaeta, Bruno A., Rimmer, Janet, Sewell, William A. and Collins, Andrew M. (2014) IgE-Associated IGHV Genes from Venom and Peanut Allergic Individuals Lack Mutational Evidence of Antigen Selection. Plos One, 9 2: e89730.1-e89730.6. doi:10.1371/journal.pone.0089730


Author Wang, Yan
Jackson, Katherine J. L.
Davies, Janet
Chen, Zhiliang
Gaeta, Bruno A.
Rimmer, Janet
Sewell, William A.
Collins, Andrew M.
Title IgE-Associated IGHV Genes from Venom and Peanut Allergic Individuals Lack Mutational Evidence of Antigen Selection
Journal name Plos One   Check publisher's open access policy
ISSN 1932-6203
Publication date 2014-02-01
Year available 2014
Sub-type Article (original research)
DOI 10.1371/journal.pone.0089730
Open Access Status DOI
Volume 9
Issue 2
Start page e89730.1
End page e89730.6
Total pages 6
Place of publication San Francisco, United States
Publisher Public Library of Science (PLoS)
Language eng
Formatted abstract
Antigen selection of B cells within the germinal center reaction generally leads to the accumulation of replacement mutations in the complementarity-determining regions (CDRs) of immunoglobulin genes. Studies of mutations in IgE-associated VDJ gene sequences have cast doubt on the role of antigen selection in the evolution of the human IgE response, and it may be that selection for high affinity antibodies is a feature of some but not all allergic diseases.

The severity of IgE-mediated anaphylaxis is such that it could result from higher affinity IgE antibodies. We therefore investigated IGHV mutations in IgE-associated sequences derived from ten individuals with a history of anaphylactic reactions to bee or wasp venom or peanut allergens. IgG sequences, which more certainly experience antigen selection, served as a control dataset.

A total of 6025 unique IgE and 5396 unique IgG sequences were generated using high throughput 454 pyrosequencing. The proportion of replacement mutations seen in the CDRs of the IgG dataset was significantly higher than that of the IgE dataset, and the IgE sequences showed little evidence of antigen selection. To exclude the possibility that 454 errors had compromised analysis, rigorous filtering of the datasets led to datasets of 90 core IgE sequences and 411 IgG sequences. These sequences were present as both forward and reverse reads, and so were most unlikely to include sequencing errors. The filtered datasets confirmed that antigen selection plays a greater role in the evolution of IgG sequences than of IgE sequences derived from the study participants.
Keyword Human-Immunoglobulin Heavy
Somatic Hypermutation
Rhinitis Patients
Transcripts
Disease
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2015 Collection
School of Medicine Publications
 
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